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Lookup NU author(s): Dr Oksana Pogoryelova
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2024 – The authors. Published by IOS Press.Introduction: GNE myopathy is a rare slowly progressive adult-onset distal myopathy with autosomal recessive inheritance. It has distinctive features of quadriceps sparing with preferential anterior tibial involvement. Most patients eventually become wheelchair bound by 10–20 years after onset. This study analyzes the phenotype-genotype characteristics and disease progression in a large cohort of GNEM patients from India. Materials and methods: Retrospective observational study on GNEM from a quaternary neurology referral hospital in southern India. Data was collected from clinical phenotyping, serum creatine kinase levels, muscle biopsy histopathology, genetic analysis and functional assessment scales – IBMFRS and MDFRS. Results: 157 patients were included with mean age at onset and diagnosis: 26.5 ± 6.2 years and 32.8 ± 7.8 years, respectively. M:F ratio was 25: 13. Most common presenting symptom: foot drop (46.5%) and limb girdle weakness (19.1%). Wasting and weakness of small muscles of hand and finger flexors seen in 66.2% and as an initial symptoms in 5.2%. Though tibialis anterior involvement was most common (89.2%), early quadriceps weakness was noted in 3.2% and Beevor’s sign in 59.2%. Rimmed vacuoles were present in 75% of patients with muscle biopsy. Most common variant was the Indian Founder variant identified in 129 patients (c.2179 G>A, p.Val727Met - 82.2%) and most common zygosity being compound heterozygous state (n = 115, 87.5%). Biallelic kinase domain variations predisposed to a more severe phenotype. Wheelchair bound state noted in 8.9% with a mean age and duration of 32.0 ± 7.1 and 6.3 ± 4.9 years respectively, earlier than previous studies on other ethnic groups. Conclusion: This is the largest GNEM cohort reported from South Asia. The p.Val727Met variant in compound heterozygous state is noted in majority (82.2%) of the cases. Observed relationships between genotype and clinical parameters shows that severity of the disease might be attributable to specific GNE genotype and thus could aid in predicting the disease progression.
Author(s): Baskar D, Reddy N, Preethish-Kumar V, Polavarapu K, Nishadham V, Vengalil S, Nashi S, Sanka SB, Bardhan M, Huddar A, Unnikrishnan G, Harikrishna GV, Gunasekaran S, Thomas PT, Keerthipriya MS, Girija MS, Arunachal G, Anjanappa RM, Nishino I, Pogoryelova O, Lochmuller H, Nalini A
Publication type: Article
Publication status: Published
Journal: Journal of Neuromuscular Diseases
Year: 2024
Volume: 11
Issue: 5
Pages: 959-968
Online publication date: 03/09/2024
Acceptance date: 10/06/2024
Date deposited: 23/09/2024
ISSN (print): 2214-3599
ISSN (electronic): 2214-3602
Publisher: IOS Press BV
URL: https://doi.org/10.3233/JND-230130
DOI: 10.3233/JND-230130
Data Access Statement: Data will be available on request from the corresponding author.
PubMed id: 39213088
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